An atypical presentation of hypothyroidism with extremely exaggerated functional impairment

Key Clinical Message Myopathy‐related symptoms are rare manifestations of hypothyroidism. Clinicians should consider hypothyroid myopathy as one of the possible diagnoses for patients with proximal weaknesses. Abstract Myopathy‐related symptoms are rare manifestations of hypothyroidism. Clinicians should consider hypothyroid myopathy as one of the possible diagnoses for patients with proximal weaknesses. We report a 34‐year‐old woman, presenting with a new atypical musculoskeletal manifestation of hypothyroidism mimicking polymyositis.

the past 2 months. She complained of an insidious proximal weakness in both upper and lower limbs 2 months ago. Her hips, thighs, shoulders, and neck were all involved with progressively worsening pain to the extent of being hardly able to hair combing, picking up her child, climbing the stairs, and even walk. She also complained of constipation and generalized abdominal pain over past 2 months. In physical examination, evaluating the force of limbs out of 5, the upper limb in proximal part got 3 and the distal part scored 5. The lower limb proximal and distal parts ranked 3 and 5, respectively. Moreover, the force of cervical flexor muscle reached 4. Before the crisis, she stated that she had no functional impairment. Her past medical history was negative, and she declined any family history of rheumatologic disorders or the same symptoms.
High levels of CPK, aldolase, and LDH at first presentation (Table 1), as well as her first clinical presentation, led to a possible diagnosis of inflammatory myopathies such as polymyositis, and immune-mediated necrotizing myopathy. We ordered pulse methylprednisolone therapy to avoid further inflammatory complications before the results of preclinical assessment get ready, however, hypothyroidism myopathy according to her TSH levels kept us waiting for the results of further evaluations. Consequently, we started oral levothyroxine 1.6mcg/kg/ day as the patients weighted 80 kgs, which is approximately equivalent to 150 microgram/day. Although intravenous (IV) levothyroxine is the choice in these conditions with severe manifestations, we had to start oral therapy since IV levothyroxine was not available.
Microscopic findings of biopsy of quadriceps skeletal muscle were as follows ( Figure 1): skeletal muscle with mild variation in size of myofibers, few nuclear centralizations and mild increased sarcolemmal nuclei, also a few degenerated and pale myofiber with a few lymphocytic inflammations around small vessels. According to pathological reports, diagnosis was nonspecific myopathy, thus we did not start acute polymyositis treatment. Continuing the observations, during her admission, CPK, LDH, and creatinine concentrations retained higher than reference range (Table 1), however, gradual decrease was found after starting thyroid hormone therapy.
Considering microscopic findings, this case was suggestive for myopathy of hypothyroidism, and the patient was discharged prescribed with levothyroxine 150 microgram/day. Her follow-up in 1 month had TSH = 14.06 μIU/L (0.4-4.2) and after 2 months, her laboratory test indicated TSH = 0.7 μIU/L (0.35-6) and free T4 = 1.6 μg/dL (0.7-2.0), and she had normal muscle enzymes and physical examination, and all the symptoms disappeared along with TSH decrease.

| DISCUSSION
Muscle involvement is a prevalent problem in both congenital and adult hypothyroidism, which can vary intensively. 3 Regardless of the fact that these were rarely the initial symptoms of the disease, in a limited sample, 79% of patients with recently diagnosed hypothyroidism experienced of weakness, fatigue, cramps, and myalgias. 4 Our case, although similar to previous reports in generalized weakness and progressive myalgia, she was the first case presenting with polymyositis typical signs and symptoms caused by hypothyroidism. Nonspecific muscle stiffness or diffuse muscle pain are frequent symptoms of hypothyroidism, which may be in correlation with an increase in the levels of muscle enzymes 5 ; however, to date, there is no report of inability to walk or complete functional impairment. In line with our patient's symptoms, proximal muscle weakness gradually increases in time. Hypothyroid myopathy can occasionally be more severe and accompanied by a noticeable rise in muscle enzymes. 6  some cases, the level of CPK is not directly related to the severity of clinical symptoms. 8 The exact mechanism of hypothyroid-associatedmyopathy remains uncertain. T4 deficiency causes disturbances in glycogenolysis and mitochondrial oxidative metabolism. Consequently, resulting in muscular dysfunction. 9 One of the manifestations is specific atrophy of type 2 fibers, which are more reliant on glycolysis for their energy source. Rhabdomyolysis of muscle cells can happen with severe or persistent oxidative damage. 10 Several cases of extremely severe rhabdomyolysis associated with hypothyroidism have been documented. 11,12 A hypothyroid evaluation is necessary if any of the aforementioned symptoms or signs cannot be explained by other identified causes. EMG could be helpful in order to distinguish hypothyroid myopathy from inflammatory myositis or other neuromuscular disorders. Nearly 50% of hypothyroid individuals with proximal muscle weakness have normal EMGs, and the rest may show myopathic alterations with an increased low amplitude, polyphasic potentials, and rarely increased insertional activity. 13 Muscle F I G U R E 1 Microscopic findings of biopsy of quadriceps skeletal muscle; (1,2): mild variation in size of fiber, nuclear sarcolemmal proliferation, (3,4): few lymphocytic infiltrations around small arteries, (5): basophilic change in a few fibers' arteries. biopsy is usually normal or may contain a few nonspecific changes such as Mild, focal necrosis, degeneration of muscle fibers and mild inflammatory infiltrates. Indeed, extensive inflammatory changes can suggest an alternative diagnosis such as polymyositis. 14 Thyroid hormone replacement therapy is efficient in treating hypothyroid myopathy. Within a few weeks, the serum CPK level would return to normal range after a rapid decline, even earlier than TSH. 15 Notably, clinical symptoms considering muscular weakness, recover more slowly. 5 In this report, normal physical examinations, muscle enzymes, and disappearance of symptoms after 2 weeks of levothyroxine therapy also confirmed hypothyroid myopathy. Thus, considering hypothyroidism as one of possible differential diagnosis in patients presenting with myopathy symptoms even very severe such as impaired gait should be considered along with inflammatory or neurological diseases.

| CONCLUSION
Hypothyroidism with the first presentation mimicking inflammatory myopathies, called hypothyroidism myopathy, is very rare. Currently, we reported the first case of gait and functional impairment, showing progressive pattern in 2 months. Practitioners should precisely consider hypothyroidism as one of the first differential diagnosis while facing high muscle enzymes and recent proximal weakness in order to avoid further unnecessary evaluations and cost in the clinic.

FUNDING INFORMATION
This research was not funded.